Abstract
Adeno-associated virus type2 (AAV-2) binds to heparan-sulfate proteoglycans on the cell surface. In vivo, attachment of viral particles to cells adjacent to the injection tract limits the distribution of AAV-2 when infused into the CNS parenchyma and heparin co-infusion might decrease the binding of AAV-2 particles to cells in the vicinity of the infusion tract. We have previously shown that heparin co-infusion combined with convection enhanced delivery enhances distribution of the GDNF family trophic factors (heparin-binding proteins) in the rat brain. In this work we show that heparin co-infusion significantly increases the volume of distribution of AAV-2 as demonstrated by immunoreactivity to the transgene product 6 days after infusion into the rat striatum.
MeSH terms
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Animals
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Anticoagulants / pharmacology*
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Brain / drug effects*
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Brain / metabolism
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Brain / virology
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Convection
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism
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Corpus Striatum / virology
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Dependovirus / drug effects*
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Dependovirus / physiology
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Drug Delivery Systems
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Female
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Functional Laterality / drug effects
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Functional Laterality / physiology
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Gene Expression Regulation, Viral / drug effects
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Gene Expression Regulation, Viral / physiology
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Gene Transfer Techniques*
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Genes, Reporter / genetics
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Genetic Therapy / methods*
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Genetic Vectors / drug effects*
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Genetic Vectors / pharmacology
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Glial Fibrillary Acidic Protein / metabolism
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Heparin / pharmacology*
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Immunohistochemistry
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Neurons / drug effects
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Neurons / metabolism
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Neurons / virology
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Rats
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Rats, Sprague-Dawley
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Thymidine Kinase / genetics
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Thymidine Kinase / metabolism
Substances
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Anticoagulants
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Glial Fibrillary Acidic Protein
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Heparin
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Thymidine Kinase